Safety and feasibility study of using Polyphosphate (PolyP) in alveolar cleft repair, A Pilot study.

Abstract Background: Bone grafting is an important surgical procedure to reconstruct alveolar bone defects in patients with cleft lip and palate. Polyphosphate (PolyP) is a physiological polymer present in blood, primarily in platelets. PolyP is playing a role as phosphate source in bone calcium phosphate deposition. Moreover, the cleavage of high-energy bonds to release phosphates provides local energy necessary for regenerative processes. In this study, polyP is complexed with calcium to form Calcium polyP microparticles (Ca-polyP MPs), which were shown to have osteoinductive properties in preclinical studies. The aim of this study was to evaluate the feasibility, safety and osteoinductivity of Ca-polyP MPs in-first human clinical trial. Methods: This single blinded, randomized, prospective clinical pilot study enrolled eight adolescent patients (mean age 18.1: range 13 - 34 years) with residual alveolar bone cleft. Randomization in two groups (four receiving Ca-polyP MPs only, four a combination of Ca-polyP MPs and biphasic calcium phosphate (BCP)) was performed. Patient follow-up was six months. Outcome parameters included safety parameters and close monitoring of possible adverse effects using radiographic imaging, regular blood tests, and physical examinations. Results: Due to surgical and technical reasons, eventually only 2 patients received Ca-polyP MPs, and the others the combination graft. All patients were assessed up to day 90. Four out of eight were able to continue with the final assessment day (day180). Three out eight were unable to reach the hospital due to Covid-19 restrictions. One patient decided not to continue with the study.No allergies or remarkable local or systematic reaction were noticed in all patients. Radiographically, patients receiving Ca-polyP MPs only were scored grade IV Bergland scale, while patients received combination Ca-polyP MPs and BCP were ranged from score I to III. Conclusions: Ca-polyP MPs and combination of Ca-polyP MPs/BCP are safe graft materials, however, Ca-polyP MPs alone are not sufficiently stable defect-filling scaffolds to be used in alveolar cleft repair. Trial registration: Indonesian Trial Registry under number INA-EW74C1N by the ethical committee of Faculty of Medicine, Hasanuddin University, Makassar, Indonesia with code number 1063/UN4.6.4.5.31/PP36/2019